Depression ketamine

Ketamine (Ketalar) is a rapid-acting general anesthetic. It produces an anesthetic state characterized by profound analgesia, cardiovascular and respiratory stimulation, normal or enhanced skeletal muscle tone, and occasionally mild respiratory depression. Ketamine is used for diagnostic and surgical procedures that do not require relaxation of skeletal muscles, for induction of anesthesia before the administration of other anesthetic drugp, and as a supplement to other anesthetic drags. 

At low doses, ketamine may result in impairment of attention, learning ability, and memory, and at high doses it has been associated with delirium, amnesia, impaired motor function, hypertension, depression, and respiratory depression (Krystal et al. 1994). Another mechanism of action appears to be a blocking of the reuptake of catecholamines. This effect leads to an increase in heart rate and blood pressure (Reich and Silvay 1989). 

Figure 1 illustrates the dose-dependent effects of ketamine on these three endpoints. A dose of 20 mg/kg significantly delayed tonic limb extension but did not protect against the lethality associated with this severe convulsive response. Higher doses significantly delayed the initial clonic convulsive response and prevented tonic limb extension. At these doses, the tonic extension response was replaced-with the abrupt onset of continuous clonic limb convulsions, which persisted until death from apparent respiratory depression. The onset of the continuous clonic convulsions and lethality was also delayed in a dose-dependent manner, at the higher doses of ketamine. 

On the other hand, the results using the hippocampal seizure model revealed an interesting profile of anticonvulsant effects for PCP and ketamine, compared to several classical anticonvulsant compounds. When tested against the unkindled hippocampal seizure, the effects of behaviorally equivalent doses of PCP and ketamine were remarkably similar, but differed substantially from the effects of the anticonvulsant drugs. The compression of the entire EEG seizure episode to a shorter duration was unique to PCP and ketamine, and suggests an anticonvulsant effect. Conversely, the small prolongation of the initial AD episode, and the decreased duration of the postictal depression, could be reflective of pro-convulsive influences. There were, however, no other indications of enhanced seizure activity, such as the appearance of motor convulsions or spread of seizure activity to the cerebral cortex. 

Papp M, Moryl E (1996) Antidepressant-like effects of 1-aminocyclopropanecarboxylicacid and D-cycloserine in an animal model of depression. Em J Pharmacol 316 145-151 Park KM, Max MB, Robinovitz E, et al (1995) Effects of intravenons ketamine, alfentanil, or placebo on pain, pinprick hyperalgesia, and allodyniaprodncedbyintradermal capsaicin in human subjects. Pain 63 163-172... 

Ketamine also can be contrasted to other intravenous drugs in its ability to cause cardiovascular stimulation rather than depression. The observed increases in heart rate and blood pressure appear to be mediated through stimulation of the sympathetic nervous system. In a healthy, normovolemic, unpremedicated patient, the initial induction dose of ketamine maintains or stimulates cardiovascular function. In contrast, patients with... 

The drug increases the heart rate, cardiac output and blood pressure which is due to sympathetic stimulation. Respiration is not depressed, muscle tone increases and reflexes are not abolished during anaesthesia. Ketamine has been recommended for short operations, unpleasant therapeutic and diagnostic procedures in children, operation in shocked patients and in obstetrics. 

Although ketamine produces direct myocardial depression, it has significant indirect cardiovascular effects through sympathomimetic effects and stimulation of the vasomotor centre. The heart rate and systolic blood pressure increase by 30% and occasionally up to 100%. Owing to the increased cardiac work and myocardial consumption, ketamine adversely affects the balance between myocardial oxygen supply and demand. Consequently, it is not recommended for use as the sole agent in adults with severe cardiovascular disease. However, the same haemodynamic effects, particularly the raised systemic vascular resistance, make the agent particularly suitable for children with cyanotic heart disease. 

In very large quantities, DXM can cause effects similar to those of ketamine and PCP because these drugs affect similar sites in the brain. These effects can include impaired motor function, numbness, nausea/vomiting, and increased heart rate and blood pressure. On rare occasions, hypoxic brain damage—caused by severe respiratory depression and a lack of oxygen to the brain—has occurred due to the combination of DXM with decongestants often found in the medication. 

Depressants account for 1 per cent of global seizure cases and other drugs for 4 per cent. This includes substances such as methaqualone, khat, various synthetic narcotics, LSD, ketamine, various non-specified psychotropic substances, and inhalants. Some of these substances (such as khat, ketamine and some of the psychotropic substances) are not under international control, but are under national control in several Member States. 

Treatment for ketamine dependence may involve psychotherapy or a 12-step program. Antidepressants may be used to treat depression that resulted in the drug use. 

Among the drugs which are known to interact with barium, the barbiturates sodium pentobarbital and phenobarbital were found to have an increased depressive effect on the hearts of rats exposed to barium (Kopp et al. 1985 Perry et al. 1983, 1989). This hypersensitivity of the cardiovascular system to anesthesia was not observed in similarly treated animals that were anesthetized with xylazine plus ketamine. Results of the study indicated that the hypersensitivity was specific to the barbiturates and not a generalized effect of anesthesia (Kopp et al. 1985). 

The belladonna alkaloids are much more toxic than the indoles and phenethylamines. Furthermore, they are just plain dangerous, and the experiences they give are, at best, difficult to integrate with ordinary consciousness. Kava-kava seems to me more like alcohol than like the psychedelics, as does nitrous oxide, a general anesthetic with similar depressant qualities. PCP and ketamine are pharmacological curiosities, not related to other recreational drugs. Many users like the "dissociative" states they provide, but few find them truly psychedelic. Their toxicity and abuse potential are significant. 

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